Hellman S, Botnick L E, Hannon E C, Vigneulle R M
Proc Natl Acad Sci U S A. 1978 Jan;75(1):490-4. doi: 10.1073/pnas.75.1.490.
The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferative quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cell progress in the continuum in one direction and such progression is not reversible.
本研究表明，随着小鼠造血干细胞的连续传代，其自我更新能力下降。分化细胞后代的产生维持时间比干细胞自我更新的时间更长。在正常动物中，自我更新能力不会随着供体年龄的增加而下降。正常动物（无论年轻还是年老）的干细胞区室似乎处于增殖静止状态。在从烷化剂白消安造成的损伤中明显恢复后，干细胞自我更新的概率降低，骨髓进行连续移植的能力出现永久性缺陷，并且干细胞具有增殖活性。这些发现支持了一种造血干细胞区室模型，即造血干细胞区室是一个连续的细胞群体，其自我更新能力逐渐下降，分化可能性增加，增殖活性增强。细胞在这个连续统一体中朝着一个方向发展，且这种发展是不可逆的。
